tbuckley/cabot-search huggingface dataset:
First-line pembrolizumab plus platinum-pemetrexed in metastatic non-small cell lung cancer: Clinical experience in a Spanish tertiary hospital.
Authors: Lara Lombardero, Ibone De Elejoste, Raquel Casas, Josune Azcuna, Berezi Ortega, Failah Mohamed Lamin, Pablo Jiménez Labaig, Itziar Rubio, Alberto Munoz Llarena, Eider Azkona
Journal: Journal of Clinical Oncology (2023)

e21142 Background: In the phase III trial KEYNOTE-189 first-line pembrolizumab (pembro) plus platinum-pemetrexed (pem) significantly improved OS and PFS in metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR/ALK alterations. We report outcomes of real-world patients (pts) treated with first line pembro plus platinum-pem in our hospital. Methods: We have done a descriptive, retrospective, single center study developed in a Spanish tertiary hospital where patients with metastatic nonsquamous NSCLC treated with first-line pembro plus platinum-pem have been included. SPSS v23 software has been used to analyze clinical data for OS and PFS using the Kaplan-Meier method. PFS-2, defined as time from first treatment to objective tumor progression on next-line treatment or death from any cause, whichever occurred first, was also recorded using the Kaplan-Meier method. Adverse events (AEs) were graded according to CTCAE v5.0. Results: From December 2019 to May 2022, 79 pts (67.1% M, 26% W; 64y median age, ECOG 0, 1, 2: 5.1%; 88.6% and 6.3%; PD-L1 &lt; 1% 36 [45.6%], PD-L1 1-49% 37 [36.8%], PD-L1 50% 3 [3.8%]; unknown PD-L1 3 [3.8%]; 95% adenocarcinoma) were assessed. After a median follow-up of 19 months, OS was 17 months (5.3-28.7). Stratified by PD-L1 expression, mOS was 9 months (6.3 -11.7) in PD-L1 &lt; 1%; 25 months in PD-L1 1-49%, NR in the rest. Median PFS was 9 months (5.8-12.2). According to PD-L1 expression, mPFS was 6 months (4.6 - 7.4) in PD-L1 &lt; 1%; 19 months (8.7 - 29.2) PD-L1 1-49% and 7 months (0.6 - 13.4) in PD-L1 50%. PFS-2 was 17 months (10.7 - 23.3). At the time of the cut off 66 pts (83.5%) had discontinued treatment: 35 (53%) due to progression, 23 (34.8%) due to toxicity; 2 (3%) due to both, and 6 (9.1%) due to other reasons. Grade 3-5 AEs were observed in 35/79 pts (44.3%). 15.2% pts needed dose-reduction and 32.6% glucocorticoids. Conclusions: First-line treatment with pembro plus platinum-pem has demonstrated benefit in terms of OS, PFS and PFS-2 with tolerable adverse effects. The results obtained in our hospital, taken together, are consistent with those published in KEYNOTE-189 trial. However, the survival of our pts with PD-L1 &lt; 1% seems to be poorer. This finding could be explained by the short median follow-up, low number of patients and differences in baseline demographic characteristics.
Patients with breast cancer and the threat of septicemia.
Authors: Kamil Taneja, Karan Patel, Michael J. Diaz, Sahas Chandragiri, Haley Hsiung, Jules A. Cohen
Journal: Journal of Clinical Oncology (2023)

e18622 Background: A very dangerous complication that can occur in breast cancer patients is septicemia. However, there are not many large scale studies that have demonstrated patient and hospital factors associated with higher risk of this complication in breast cancer patients. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to identify breast cancer patients that presented to the emergency department (ED) with a primary diagnosis of septicemia. A multivariate logistic regression was used to identify characteristics that were significantly associated with a higher chance of septicemia. A p-value less than 0.05 was considered significant. Results: Between 2006 and 2012, 2,160,701 breast cancer patients presented to the ED. Out of these patients, 39,164 (1.8%) presented to the ED with a primary diagnosis of septicemia. Most patients were at least 80 years old (61.5%), female (98.9%), Medicare beneficiaries (73.8%), of the highest income quartile (28.6%), living in the South (34.3%), presented to non-trauma hospitals (51.5%), and presented to metropolitan non-teaching hospitals (46.0%). Factors associated with the highest risk of septicemia in breast cancer patients are the following: Medicaid patients (odds ratio (OR): 2.0, 95% Confidence Interval (CI): 1.6-2.6, p &lt; 0.001), Medicare patients (OR: 2.0, 95% CI: 1.6-2.5, p &lt; 0.001), private insurance patients (OR: 1.7, 95% CI: 1.4-2.1, p &lt; 0.001), living in the West (OR: 1.5, 95% CI: 1.3-1.7, p &lt; 0.001), living in the Northeast (OR: 1.3, 95% CI: 1.1-1.5, p &lt; 0.001), presenting to a metropolitan non-teaching hospital (OR: 1.2, 95% CI: 1.1-1.4, p = 0.03), and presenting to a metropolitan teaching hospital (OR: 1.3, 95% CI: 1.1-1.5, p = 0.003). Almost all breast cancer patients with septicemia were admitted (97.6%), discharged the same day (1.0%), or transferred to a short-term hospital (0.7%). Amongst patients that were admitted, most patients were discharged (34.4%), transferred to a skilled nursing facility or intermediate care facility (29.8%), or died (16.2%). Risk factors associated with increased risk of dying in septicemia patients are the following: living in the Northeast (OR: 1.4, 95% CI: 1.2-1.8, p = 0.001), presenting to a metropolitan teaching hospital (OR: 1.3, 95% CI: 1.0-1.7, p = 0.046), and living in the South (OR: 1.2, 95% CI: 1.0-1.5, p = 0.045). Conclusions: After correcting for patient and hospital characteristics, a patient’s insurance status, the hospital’s region, and the hospital’s teaching status are intimately related to a breast cancer patient's risk to develop septicemia. Furthermore, hospital region and teaching status are also associated with a breast cancer patient’s risk of dying from septicemia. This suggests that a patient’s access to resources is critical for their risk of developing cancer-related complications.
Effect of lymph node dissection and adjuvant therapy in patients with sentinel node+ melanoma: An observational multicenter study.
Authors: Dai Ogata, Mai Iwata, Hiroshi Kato, Satoshi Fukushima, Takeo Maekawa, Yasuhiro Nakamura, Arata Tsutsumida, Takayuki Suyama, Hiroshi Kitagawa, Yoshio Nakamura, Tatsuya Takenouchi, Shigeto Matsushita, Kohei Oashi, Junji Kato, Susumu Fujiwara, Taku Maeda, Aya Nishizawa, Yu Kawahara, Naoya Yamazaki, Kenjiro Namikawa
Journal: Journal of Clinical Oncology (2023)

e21569 Background: Currently, lymph node dissection (LND) is not mandatory for patients with sentinel node (SN)+ melanoma. Anti-programmed cell death receptor-1 (PD-1) monotherapy and dabrafenib/trametinib combination (for BRAF mutations) are standard adjuvant treatments for patients who undergo definitive surgery for melanoma. However, the effects of this approach remain unclear in patients with stage III melanoma in real-world clinical settings. We investigated the effects of the aforementioned therapeutic approaches on the prognosis of stage III melanoma in a Japanese cohort. Methods: We retrospectively analyzed clinical data of patients with SN+ melanoma treated with or without anti-PD-1 monotherapy or combination dabrafenib/trametinib therapy obtained from 39 independent institutions in Japan between 2018 and 2021. Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were compared with regard to LND, adjuvant therapy type, and clinical factors. Results: We investigated 357 patients; 35.9% (128/357) of patients underwent LND, of whom 70.3% (90/128) received adjuvant therapy. LND was not performed in 64.1% (229/357) of patients, of whom 74.7% (171/229) received adjuvant therapy. RFS and OS did not differ between patients with and without LND (2-year RFS 54.5% vs. 51.5%, p = 0.98; 2-year OS 84.1% vs. 86.5%, p = 0.39). RFS and OS did not differ between patients with and without adjuvant therapy (2-year RFS 54.5% vs. 50.4%, p = 0.90; 2-year OS 83.4% vs. 89.8%, p = 0.33). Multivariate analysis of RFS after adjustment for adjuvant therapy, clinical subtype, tumor thickness, ulceration, and BRAF status showed significant differences between patients with and without adjuvant therapy (hazard ratio 3.06 [95% confidence interval 1.39–6.76]). Data analysis in 261 patients who received adjuvant therapy showed no difference between patients with and without LND (2-year RFS 55.9% vs. 52.6%, p = 0.74; 2-year OS 83.4% vs. 83.6%, p = 0.73). Regarding adjuvant therapy type, RFS and OS were significantly longer in patients who received BRAF/MEK inhibitors than in those treated with PD-1 monotherapy (2-year RFS 75.0% vs. 42.2%, p &lt; 0.01; 2-year OS 89.3% vs. 79.5%, p = 0.01). Conclusions: Our study revealed that LND did not affect prognosis and adjuvant therapy reduced the recurrence of stage III melanoma in a Japanese cohort. Although the follow-up period was short, with regard to drug selection, RFS and OS were significantly longer in patients treated with BRAF/MEK inhibitors than in those who received PD-1 monotherapy. Factors contributing to the lower effectiveness of PD-1 monotherapy remain unclear and warrant further investigation.
Outcomes of patients with multiple myeloma refractory to different administration schedules of bortezomib.
Authors: Utkarsh Goel, Charalampos Charalampous, Prashant Kapoor, Moritz Binder, Francis Buadi, David Dingli, Angela Dispenzieri, Amie L. Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi Lisa Hwa, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2023)

e20011 Background: Drug refractoriness is an important factor determining choice of next therapy and prognosis in multiple myeloma (MM). It is debatable whether refractoriness to a drug varies among patients (pts) with MM progressing on different administration schedules of the drug. Outcomes of MM pts refractory to different doses of lenalidomide have been previously described, but similar data about proteasome inhibitors (PIs) are limited. In this study, we assessed the impact of refractoriness to different schedules of bortezomib (V) on outcomes with subsequent therapies in MM pts. Methods: We retrospectively reviewed MM pts at our center diagnosed between January 2004 and December 2018, who progressed on/ after receiving first line therapy with V containing regimens. At first relapse, we divided pts into 3 groups- MM progressing on or within 60 days of receiving (1) 1-1.3 mg/m 2 V once weekly or more frequently (Standard Dose Refractory), (2) 1-1.3 mg/m 2 V once every 2 weeks or less frequently (Low Dose Refractory), and (3) MM progressing at least 60 days after stopping V (Not Refractory). In addition to V, we classified pts as being refractory to cyclophosphamide and immunomodulatory drugs (IMiDs) at first relapse. We classified salvage regimens into daratumumab (Dara), PI, IMiD, PI+IMiD, and VDTPACE like regimens. We then assessed progression free survival (PFS) and overall survival (OS) for next line therapy, and for next V containing therapy using Kaplan Meier and Cox models. Results: A total of 302 pts were included. Median age at diagnosis was 62 years and 60% pts were male. Overall, 23%, 31%, and 27% were International Staging System (ISS) stage I, II, and III respectively; 40% had high risk FISH as per mSMART. Of the 302 pts, 134 (44%) pts received another V containing regimen after the first line therapy at any time during the disease course. Using a multivariable Cox model to adjust for ISS, high risk FISH, refractoriness to other drugs, duration of first line therapy, and treatment received at relapse, the Not Refractory Group had a better PFS for both 2 nd line therapy and the next V containing line of therapy, while no significant differences were seen between the Standard Dose Refractory and Low Dose Refractory groups. OS differences followed the same trend but were not statistically significant (Table). Conclusions: On multivariable analysis, the PFS did not differ among standard dose vs low dose refractory pts, and both were significantly inferior to pts not refractory to V. These data suggest that refractoriness to V might not be a dose dependent phenomenon. [Table: see text]
Class II and class III <i>BRAF</i> mutations in patients with advanced non-small cell lung cancer (NSCLC): Clinical characteristics, mutation patterns, and survival outcomes.
Authors: Anna Rasokat, Anna Kron, Lucia Nogova, Udo Siebolts, Heather Scharpenseel, Richard Riedel, Sebastian Yves Friedrich Michels, Rieke Nila Fischer, Anna Eisert, Darinka Prang, Frank Beckers, Kato Kambartel, Britta Kaminsky, Bernhard Schaaf, Wolfgang Schulte, Monika Heidi Serke, Sabine Merkelbach-Bruse, Reinhard Buettner, Juergen Wolf, Matthias Scheffler
Journal: Journal of Clinical Oncology (2023)

e21204 Background: Class II and class III BRAF mutations (i. e., non-V600X) in NSCLC differ from V600E in terms of dimerization and KRAS-dependency. Whereas V600X is effectively targetable by combined BRAF- and MEK-inhibition, no specific targeted approach for non-V600X exists, and a comprehensive description of the patient group is lacking. This retrospective cohort analysis presents clinical and genomic characteristics of a large cohort of patients with advanced BRAF nonV600X mutant lung cancer. Methods: Molecular data of 1411 lung cancer patients staged IIIb/IV and harboring BRAF mutations were linked to hospital registry data in the NGM (Network Genomic Medicine) database. Biospecimens were analyzed using next-generation sequencing (NGS). Results: 721 patients with BRAF non-V600X mutations were identified, of whom 10.5% had been diagnosed with squamous cell carcinoma (SCC) and 89.5% had non-squamous histology. Median age at diagnosis was 66 years (range: 34-81) and the cohort comprised 409 (56.7%) men and 312 (43.3%) women. 301 (41.8%) of the BRAF non-V600X alterations detected in this cohort are “activators” in the MAPK pathway (class II, including G469A/V/R, G464A/E/L/V, K601E/N, L597Q/R/V), while 310 (43.0%) function as “amplifiers” (class III, including mutants such as D594A/G/H/N, G466A/E/V, G469E, N581I/S/T in this cohort). While 21.5 % (155; SCC: 12.3%; non-SCC: 22.9%) of patients did not have any co-occurring mutations (55.6% of SCC and 37.1% of non-SCC patients respectively), TP53 was the most frequent co-mutation, detected in 56.6% (SCC: 74.0%; non-SCC: 53.8%) of patients. 16.4% (118) exhibited a KRAS co-mutation (SCC: 4; non-SCC: 109). A preliminary survival analysis suggests no significant difference in overall survival between these broad classes (HR 0.92, 95%-CI 0.62, 1.36). Conclusions: The study highlights the heterogeneity of patients with BRAF class II and class III regarding histology and co-mutational status, with both classes equally frequent. A more granular investigation of non-V600X alterations and their associated clinical outcomes under different treatment approaches is ongoing.
Global burden and economic impact of vaccine-preventable cancer mortality.
Authors: Goran Bencina, Edward Oliver, Anne Meiwald, Robert Hughes, Edith Morais, Julia A Schillinger, Georgie Weston
Journal: Journal of Clinical Oncology (2023)

10542 Background: Cancer has a high clinical and economic burden, with ~10 million deaths globally in 2020. In Europe, the total cost of cancer was €199 billion in 2018. Infections are responsible for approximately 13% of cancer cases worldwide. Human papillomavirus (HPV) and hepatitis B (HBV) are among the most important infections associated with cancer for which vaccines are available. However, global vaccination rates for these cancer-causing infections remain low (~12% for HPV; 42% for HBV). Elimination of vaccine-preventable cancers is a public health priority, and the World Health Organization (WHO) has proposed a strategy to eliminate cervical cancer and viral hepatitis by 2030. This analysis aims to estimate the global burden and economic impact due to vaccine-preventable cancer mortality. Methods: The number of deaths and Years of Life Lost (YLL) in 2019 from liver cancer caused by hepatitis B (ICD-10 C22), head and neck cancers (ICD-10 C00-14 and C32), and cancer of the cervix uteri (ICD-10 C53) were sourced from the Institute for Health Metrics Evaluation (IHME) Global Burden of Disease. Deaths and YLL were applied to attributable fractions for each vaccine-preventable cancer based on published data. The Value of YLL (VYLL) was estimated by multiplying the GDP per capita (World Bank; in USD) and YLL for each cancer, in each WHO region. Sensitivity and scenario analyses were performed to test the robustness of results. Results: In 2019, there were 479,750 potentially vaccine-preventable cancer deaths and 14,561,049 YLL (38% in males) across WHO regions (Table). The estimated economic impact due to vaccine-preventable cancer deaths was over $171 billion globally with the Americas and European region accounting for 63% of the total cost ($107 billion). Cervical cancer had the highest mortality burden (52% of total deaths). Globally, 78% of non-cervical HPV-related cancer deaths were in males. Conclusions: In 2019, 1,314 people died per day due to vaccine-preventable cancers leading to substantial YLL and economic impact. The overall burden is likely to be higher since several other HPV-related cancers were not included in this analysis. Improved implementation of HPV and HBV vaccination programs should be prioritized to decrease this burden.[Table: see text]
Comparison of daratumumab-based regimens as second-line therapy in relapsed/refractory multiple myeloma.
Authors: Charalampos Charalampous, Utkarsh Goel, Prashant Kapoor, Moritz Binder, Francis Buadi, David Dingli, Angela Dispenzieri, Amie L. Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi Lisa Hwa, Taxiarchis Kourelis, Martha Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2023)

e20032 Background: The introduction of anti-CD38 antibodies (daratumumab) in the treatment landscape of multiple myeloma (MM) has increased the progression-free survival (PFS) in recent years. Still, the ideal combination (Dara-IMiD vs. Dara-PI) of these drugs in patients with relapsed MM is unclear. Methods: We reviewed MM patients treated with daratumumab as second-line therapy at our institution from 2016 to 2022 to assess the outcomes with the different combination therapies. We used the Kaplan-Meier method to estimate PFS from the first relapse. Results: We identified 329 patients with a median age of 63.6 years (range: 27.1 – 90.4). Most of the patients received triplet induction therapy (95%) and upfront transplant (67%) as primary therapy. At the time of Dara initiation, 41% were refractory to IMiDs, 22% to PIs, 18% to both, and 18% to neither drug. Patients treated with Dara-IMiD had significantly better PFS than Dara-PI (28.7 months vs. 18.5 months, p &lt; 0.01, respectively). In a subgroup analysis based on the FISH results, high-risk patients had similar PFS outcomes (24.3 vs. 10.2 months, p = NS, respectively), while standard-risk patients benefited significantly from the Dara-IMiD regimen (48.3 vs. 19.2 months, p &lt; 0.01, respectively). Among patients treated with Dara-IMiD, those already refractory to IMiDs from the first line had significantly shorter PFS than those without IMiD resistance (14.9 vs. 43.3 months, p &lt; 0.01, respectively). In addition, the lenalidomide-based combination resulted in significantly better PFS compared to pomalidomide in our cohort (40.5 vs. 19.2 months, p &lt; 0.01, respectively). However, no difference was found in the IMiD refractory population (12.3 vs. 15.1 months, respectively). Finally, no significant differences were seen between Dara-IMiD and Dara-PI in patients only refractory to IMiDs (16.1 vs. 12.8 months, p = NS, respectively). Conclusions: While further studies are required to adjudicate the best combination, we conclude that Dara-IMiD might be more effective in patients with relapsed MM, especially for patients not refractory to IMiD at first line. [Table: see text]
Evaluation of hyperprogression in patients with sarcoma treated with targeted therapy and/or immunotherapy in early-phase clinical trials.
Authors: Aisha Alshibany, Esmail Mutahar Al-Ezzi, Abha A. Gupta, Abdulazeez Salawu, Geoffrey Alan Watson, Lisa Wang, Philippe L. Bedard, Anna Spreafico, Aaron Richard Hansen, Lillian L. Siu, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2023)

11560 Background: Hyper-progressive disease (HPD) is an adverse outcome with acceleration of tumor growth, often accompanied by clinical deterioration. This phenomenon is described with immunotherapy (IT) but its incidence in sarcoma and/or in the context of targeted therapy (TT) remains unknown. Tumor growth rate (TGR) allows for dynamic evaluation of tumor volume change over time and may complement RECIST. We evaluated HPD in sarcoma patients (pts) treated in early-phase trials by assessing TGR and describing their subsequent clinical outcomes. Methods: We retrospectively reviewed medical records from advanced soft tissue sarcoma (STS) pts enrolled in early phase trials at the Princess Margaret Cancer Centre between January 2012 and December 2022. TGR was calculated based on tumor measurements taken at pre-baseline, baseline, and on-treatment CT scans. We used the Champiat formula (Clin Cancer Res 2017) to calculate TGR ratio. Primary objective was to describe the incidence of HPD, defined as a TGR ratio of &gt; 50%. Secondary objective was to investigate the correlation between HPD with progression-free survival (PFS) and overall survival (OS). Results: We identified a total of 192 pts involved in STS early phase trials from 2012-2022. Most common histology was leiomyosarcoma seen in 72 pts. Eighty-four pts (43.8%) received TT, 75 (39%) pts received IT-based, and the rest had combined TT/IT regimens (n = 33, 17.2%). The incidence of HPD was 6.8% (n = 13), including IT-based (n = 9) and non-IT-based (n = 4) regimens. HPD was associated with a worse PFS, and OS compared to non-HPD pts (median PFS 1.6m vs 4.6m HR: 5.5, 95%CI 2.8-10.6, P &lt; 0.001; median OS 5.5 vs 16.1 months; HR: 3.7, 95%CI: 2.0-7.1, P &lt; 0.001). On multivariable analysis, only IT was significantly associated with HPD (OR 3.9, 95%CI: 1.1-13, P = 0.021). There was no association between HPD and new lesions or sarcoma histology subtype. Conclusions: HPD occurs in a small subset of sarcoma patients undergoing clinical trials with TT or IT. Exploring TGR provides clinically meaningful data as it pertains to HPD as it predicts OS and PFS in sarcoma patients undergoing early-phase clinical trials.